Hydrogen: A Novel Option in Human Disease Treatment

Abstract

H₂ has shown anti-inflammatory and antioxidant ability in many clinical trials, and its application is recommended in the latest Chinese novel coronavirus pneumonia (NCP) treatment guidelines. Clinical experiments have revealed the surprising finding that H₂ gas may protect the lungs and extrapulmonary organs from pathological stimuli in NCP patients. The potential mechanisms underlying the action of H₂ gas are not clear. H₂ gas may regulate the anti-inflammatory and antioxidant activity, mitochondrial energy metabolism, endoplasmic reticulum stress, the immune system, and cell death (apoptosis, autophagy, pyroptosis, ferroptosis, and circadian clock, among others) and has therapeutic potential for many systemic diseases. This paper reviews the basic research and the latest clinical applications of H₂ gas in multiorgan system diseases to establish strategies for the clinical treatment for various diseases.

Figure 1

Biological effects of H₂. H₂ exhibits selective antioxidative and anti-inflammatory activities and can regulate ER stress, mitochondria, and immune function. H₂ selectively scavenges ^·OH and ONOO-, upregulates Nrf-2 and HO-1, and downregulates the expression of proinflammatory and inflammatory cytokines that include TNF-α, NF-κB, INF-γ, Fas, FasL, IL-1α, IL-1β, IL-6, IL-8, and IL-10, as well as downregulates ER stress-related factors that include GRP78 and TRAF2. H₂ also reduces miR-210 and activates OXPHOS in mitochondria. Finally, H₂ increases CD4+CD25+Foxp3+Treg cells and maintains the Th1/Th2 balance.

Figure 2

Various effects of H₂ on cell death. Activities of H₂ include inhibition of apoptosis, and the regulation of autophagy, circadian clock, ferroptosis, and pyroptosis.